Medicament dispensing system

ABSTRACT

A medicament dispensing system for treatment of a disease is disclosed, the system comprising: (i) detecting means for detecting one or more biochemical marker(s) indicative of the disease; (ii) electronic processing means for processing information obtainable from the detecting means; and (iii) medicament dispensing means for dispensing a quantity of medicament determinable by the electronic processing means. The medicament dispensing system is particularly useful for the treatment of respiratory disorders, such as asthma, or for other disorders which may be treated by inhalation, either through the nose or mouth.

The present invention relates to a novel medicament dispensing systemfor treatment of a disease, the system being able to provide diagnosticinformation relating to the extent and severity of the disease and beingarranged to dispense an appropriate quantity of medicament, wherein themedicament is the adjustable dosage of one or more drugs in a fixed orvariable combination.

BACKGROUND TO THE INVENTION

Many people who suffer from a chronic disease require regular medicationto ensure adequate control of the disease. For example, asthmaticsnormally require a daily dose of an anti-inflammatory drug to prevent anasthma attack. In addition, asthmatics often require a different doseand/or a different anti-inflammatory drug to treat an asthma attack. Ineach case, the amount of drug required by the patient will depend on theseverity of the asthmatic condition or the severity of asthma attack. Atpresent, a patient is supplied with an inhaler device which dispenses apre-determined quantity of medication, and which does not take intoaccount the precise present day condition of the patient. WO95/22365discloses an inhaler that measures a specific feature of the disease,for example the inhalation airflow, and processes this information toadvise the patient, inter alia, on changes in timings or dosages of drugto be taken. It is however, up to the patient to implement thesechanges. Furthermore, any changes in drug dosage will be based on thepatient's condition at the time the previous dose was administered andnot the current condition of the patient.

BRIEF SUMMARY OF THE INVENTION

It is therefore an object of the present invention to provide anintegrated medicament dispensing system that is able determine thedosage of medicament required and dispense this dosage, so that thepatient is receiving the appropriate dosage for his condition at thattime..

Accordingly, the invention provides a medicament dispensing system fortreatment of a disease, the system comprising:

-   (i) detecting means for detecting one or more biochemical marker(s)    indicative of said disease;-   (ii) electronic processing means for processing information    obtainable from the detecting means; and-   (iii) medicament dispensing means for dispensing a quantity of    medicament determinable by the electronic processing means.

In one aspect of the invention, the detecting means, electronicprocessing means and medicament dispensing means are integrated in asingle device. The device is suitably configured as a portable orhandheld device.

In another aspect, the detecting means is provided as an attachment tothe medicament dispensing means. Suitably, communication (e.g. via adocking interaction) exists between the detecting means and themedicament dispensing means.

In a further aspect, the detecting means is remote to the medicamentdispensing means. Suitably, communication (e.g. via wireless means)exists between the detecting means and the medicament dispensing means.

In a still further aspect, the detecting means and medicament dispensingmeans are integrated in a single device and the electronic processingmeans exists as a standalone unit.

DETAILED DESCRIPTION OF THE INVENTION

The medicament dispensing system herein comprises detecting means fordetecting one or more biochemical marker(s) indicative of a diseasestate.

Certain biochemical markers are indicative of a given disease and can beused to determine the current extent and severity of the disease.Examples of such biochemical markers include, but are not limited to:eicosanoids, such as prostanoids (e.g. PGE₂, PGF_(2α), TxB₂),leukotrienes (e.g. LTB4, LTC₄, LTD₄, LTE₄, LTF₄), isoprostanes (e.g.F₂-isoprostanes, 8-epi-PGF₂ (8-isoprostane)); nitric oxide relatedproducts, such as nitric oxide (NO), nitrotyrosine, nitrite (NO₂ ⁻),nitrate (NO₃ ⁻), s-nitrosothiols (SNO); hydrogen peroxide (H₂O₂); lipidperoxidation products, such as thiobarbituric acid-reactive substances,phospholipidester, cholesterylester, hydroperoxides, aldehydic lipidperoxidation products (e.g. 4-hydroxynonenal, fluorescent proteinadducts (e.g. lipofuscin), conjugated dienes and antioxidants;vasoactive amines, such as acetylcholine, serotinin, histamine,catecholamines, cortisol and thyroxine; electrolytes, such as Na⁺, Cl⁻,Mg²⁺, Ca²⁺; ammonia; hydrogen ions; proteins; cytokines, such asinterleukin-1_(β) (IL-1_(β)), interleukin-2 (IL-2), interleukin-6(IL-6), tumour necrosis factor α (TNF-α) and interleukin-8 (IL-8);carbon monoxide (CO); and exhaled hydrocarbons, such as ethane, propane,butane, pentane, isoprene. Detection and quantification of thesebiochemical markers will enable the extent and severity of the diseaseto be determined and the most appropriate dose of medication to begiven.

Suitably, the detecting means comprises a sensing means, for example abiosensor that is able to specifically detect one or more givenbiochemical markers. In general terms, ‘biosensor’ means a sensor, whichresponds to the presence of particular biochemical markers and convertsit into a correlated measurable signal.

Biosensors may generally be classified by four different principles:bioaffinity, biocatalytic, transmembrane and cell sensors. In abioaffinity sensor, the biochemical marker is recognised by immobilisedrecognition units on the sensing layer. In a biocatalytic sensor, thebiochemical marker is converted by, for example immobilised enzymes onthe sensing layer, to products. In a transmembrane sensor, eithertransport or channel proteins, or receptor proteins are incorporatedinto a membrane in the sensing layer. These structures either move thebiochemical marker through the membrane, bind the biochemical marker andopen a channel for another species or subsequently activate a separateenzymatic cascade. A cell sensor utilises immobilised living cells inthe sensing layer to either convert or bind the biochemical marker. Thevarious different types of sensors are described in more detail byZiegler and G pel in Current Opinion in Chemical Biology 1998, 2:585-591 which is incorporated herein in its entirety by reference.

Suitably, the biosensor comprises at least two main parts: a sensinglayer and a transducer layer.

The sensing layer of the biosensor suitably captures the targetbiochemical markers either by physical binding or by characteristicinteractions in a highly selective manner. The sensing layer maycomprise one or more of the following types of material: enzymes,receptors, micro-organisms, antibodies, antigens, nucleic acids, cells,peptides, proteins, biochemicals. Alternatively, artificial or syntheticmaterials analogous to those listed above may be used in the sensinglayer. Such artificial or synthetic materials may be known as‘artificial receptors’, ‘artificial antibodies’, ‘synthetic DNA’,‘synthetic peptides’ etc., for example a material known as the‘Molecularly Imprinted Polymer (MIP)’.

In one aspect, the sensing layer comprises a renewable sensing surface,i.e. the sensing surface is regenerated so that it can be used to detectthe biochemical markers more than once.

Immobilisation of the recognition units on the sensing surface isachieved by either forming a chemical bond with the surface, or byencapsulating the recognition units in a layer of porous material coatedonto the surface, such as Sol Gel, Hydro Gel, and polymer membranes. Iftransmembrane proteins are used as recognition units, they may also beembedded into a lipid membrane (or cell membrane) anchored onto thesensing surface by chemical bonds.

The sensing surface described above can be developed as aself-generating surface which can be used continuously for generation ofsensing signals in response to the presence of targeting analytes. Suchsurfaces include, typically, biocatalyst as recognition molecules. Abiocatalyst does not change its chemical and physical structures buthelps to speed up specific reaction of the analytes

Another type of renewable sensing surface requires incorporation of asurface renewing process between two sequential measurements, to removebound analytes from the recognition molecules. This is achievedtypically by changing the chemical environment of the sensing surface,e.g. the biochemical marker(s) can be removed from the sensing surfaceby lowering the pH of the sensor.

In another aspect, the biosensor comprises a removable non-renewablesensing surface. In such a scheme, the sensing surface is positioned ona removable component, which can be removed and replaced by a new one inbetween one measurement and the next.

The transducer layer of the biosensor acts such as to translate themolecular interactions, used to sense the target, into a measurablesignal. There are a range of mechanisms that may be used to realise thisconversion, for example optical, electrical, semi-conductor, thermal andacoustic. The most commonly used methods are electrochemical and opticaltransducers. The former convert biological interactions intoproportional electrical signals, and the latter into light signals.Other physical signals used include heat, sound, mass and magnetism.

In a further aspect, the sensing means comprises one or morenon-specific bio- or chemosensors, e.g. an ‘electronic nose’ (or‘electronic tongue’). Certain diseases are associated with unique bodyodour signatures, which may be useful in assessing the extent andseverity of the disease at a given time. The electronic nose uses arraysof sensing elements, typically thin film coating of, for example,polymers (e.g. conducting polymer—polypyrrole) or metal oxides, such astin oxide and zinc oxide. Each sensing element is chosen to havedifferent absorption characteristics for the biomarker(s) beinginvestigated such that a matrix array of elements can be used todeconvolute components in a test sample. Signals generated includevariations in electrical conductivity, weight/mass or acousticattenuation. Deconvolution of such overlapped responses from the sensingelement array is achieved by application of an appropriate mathematicalalgorithm (e.g. artificial neural-network or chemometrics) to generatemolecular ID(s) of biomarker(s). Therefore, the electronic nose can beused to determine mixtures of odours simultaneously or individually. Thesensing elements in an electronic nose have little specific selectivity.The specificity of an electronic nose is achieved by deconvolution of anarray of responses resulting from various sensing elements. Therefore,the technology can detect a range of molecules, determined by thematerials of sensing elements.

The absorption of gas molecules by the sensing elements of an electronicnose is a reversible process, and therefore an electronic nose can berepeatedly used over the lifetime of the sensing material.

In certain situations, a pre-separation process can be placed in frontof a non-specific sensor to separate various species within theanalytical sample, which are detected sequentially by a non-selectivesensor. Separation technologies suitable for such applications can be aminiaturised gas chromatograph device, a capillary electrophoresis chip(‘lab on a chip’), or other electrophoresis device, (such as gelelectrophoresis and free flow electrophoresis, dielectrophoreticseparation etc.), or simply, a piece of lateral flow membrane.

A number of biosensors, which are currently available, may be adaptedfor use in the medicament dispensing system of the present invention.Such biosensors include, but are not limited to: ZeptoCHIPs and ZeptoTAS(available from Zeptosens AG), BeadArray™ (available from Illumina),ProcessMonitor, MultiTRACE, Dialysis Probe etc (available from TRACEBiotech AG), SIRE Biosensors (available from Chemel AB), LIBRA α,LibraNose etc (available from Technobiochip), VOCcheck, VOCmeter etc(available from Applied Sensors), Cyranose 320 (available from CyranoSciences), Osmetech Microbial Analyser™, SENSA (available fromOsmetech), Implanted Glucose Biosensor (available from BYBD),BreathAlert™, Breath Checker (available from Comfort House), SAFE™Personal Alcohol Breath Analyzer available from Craig Medical), ZNOSE™(available from Electronic Sensor Technology), PROMETHEUS, FOX, Astree,etc (available from Alpha M.O.S.), GlucoWatch® (available from Cygnus)and The Glucose Sensor (available from Animas Corp).

In another aspect, the detecting means directly detects the presence ofthe biomarker(s) of interest.

Suitably, the detecting means comprises spectroscopic detecting meansfor direct spectroscopic detection of one or more biochemical marker(s).In variations, the spectroscopic detecting means are used in combinationwith one or more biosensors incorporating a sensing layer and transducerlayer or as an alternative thereto.

The spectroscopic detecting means may be employed in either destructiveor non-destructive methods of detection of the relevant biomarker(s) andutilise any suitable analytical methods and techniques.

Suitable non-destructive detection methods include those usingspectroscopic detecting means to detect any suitable spectralcharacteristics of the biomarker(s). Examples of suitablecharacteristics include the absorbance, reflectance, scattering,fluorescence, magnetic resonance and luminescence characteristics of thebiomarker(s). It will be appreciated that the particular spectroscopictechnique employed will be chosen in view of the properties of theparticular biomarker of interest. Particularly suitable methods includeinfra red and Raman spectroscopy.

Suitable destructive detection methods include those using varioustechniques to break up the relevant biomarker(s) into component partsthereof. The fragments are then analysed e.g. for characteristicfragmentation fingerprints. Suitable methods include gas chromatography,mass spectrometry and ion mobility spectroscopy. It will be appreciatedthat the particular method employed will be chosen in view of thebiomarker of interest and its fragmentation characteristics.

In aspects herein, plural detection methods are employed to characteriseany particular biomarker(s). In one particular aspect, plural (e.g.spectroscopic) detecting means are arranged in array fashion.

The medicament dispensing system comprises electronic processing meansfor processing information obtainable from the detecting means.

Suitably, the electronic processing means comprises a micro-controllerwith associated analogue and digital electronics, and interfaces. Theelectronic processing means receives the output electronic signal fromthe detecting means, amplifying it and converting it into appropriateanalogue or digital signal format at an electronic interface. Byanalysing the signal using an appropriate analogue computer (circuitry),or using appropriate algorithms (software) in the case of a digitalcomputer, a biomarker specific response can be determined, andcorrelated with the extent and severity of the disease at that time. Thequantity of medicament required to treat the disease can then bedetermined based on the efficacy of the drug and optimum response of thedosing curve at the severity level of the disease as measured. Thecorrelation between the disease status and the control parameters fordrug dosing are pre-determined from clinical studies and pre-stored inthe device, in the form of a series of electronic circuit settings(analogue system), or data stored in the memory in the case where adigital system is being used.

If the output signal from the detection means is not an electricalsignal, for example the signal is light (fluorescence spectra,absorption, luminescence etc), heat, acoustic, etc., an appropriatedetector based on a corresponding principle (photo-electric,thermoelectric, or acousto-electric, etc.) is used to convert the signalinto an electrical signal before it is connected to the above describedelectronics amplification, signal conditioning and processingelectronics for further analysis.

The micro-controller is typically a Single-Chip-Computer, which is aminiature computer fabricated on a single semiconductor chip, containingcentral processing unit (CPU), on board memories (e.g. RAM and EPROM),and appropriate interfaces (e.g. timer/counter, parallel digitalinterfaces, A/D, D/A interface). The single-chip-computer can beprogrammed through a system development kit. Using such a kit,appropriate components, such as a working-clock oscillator, resistors,and capacitors etc, can be tested and wired with the computer to allowthe desired functions and the software programme tested before it is‘permanently’ fixed onto the memory within the computer for systemcontrol and performing mathematical analysis. The computer will directlyconvert the analogue signal from the detection means into digitalsignals and perform mathematical analysis to extract all necessaryinformation from the signal, comparing the measured result with theresults stored in the computer database (e.g. stored within a suitableLook up table), decide and control subsequent actuation via sending outappropriate control electrical signal to the actuator. The system willalso be able to display the result via associated LED or LCD, or otherdisplay devices and communicate with other database systems via aseries/parallel interface for record and for tele-medicine purpose.

Alternately, a micro-controller can be developed based on asingle-board-computer, which integrates a central processing unit (CPU),memories (e.g. RAM, EPROM), and interfaces (A/D, D/A, Counter/ Timers,etc.) on to a single printed circuit board. It functions in much thesame manner as the single-chip-computer.

Alternatively, an analogue computer is used in place of a digitalsingle-chip or single-board computer and the signal is processed in anall-analogue form. Corresponding control signals for driving actuationmechanisms and result display are also all analogue signals.Communication with other systems is achieved via appropriate interfaces.

Suitably, there is provided an electronic data management system that iseither integral with or communicates with the electronic processingmeans. The electronic data management system typically has input/outputcapability and comprises a memory for storage of data; a microprocessorfor performing operations on said data; and a transmitter fortransmitting a signal relating to the data or the outcome of anoperation on the data.

Suitably, the medicament dispensing system additionally comprises a datainput system for user input of data to the electronic data managementsystem. Preferably, the data input system comprises a man machineinterface (MMI) preferably selected from a keypad, voice recognitioninterface, graphical user interface (GUI) or biometrics interface.

Suitably, the electronic data management system is adapted to receiveand process data relating to initial settings of any feature;medicament-related prescribing data; and data relating to the patient.The data is, for example, input to the data management system by thedoctor, nurse, pharmacist or even the patient or it may be factorypre-set. Examples of patient-related data for inputting could forexample, include the age, sex, bodyweight and the generalmedical/prescription history of the patient. Examples ofmedicament-related data could include the ‘standard’ dosage regime andpermissible variations within that regime.

Energy may be conserved by a variety of means to enable the system tooperate for longer on a given source of energy, such as a battery.Energy conservation or saving methods have additional advantages interms of reducing the size requirements of the power source (e.g.battery) and thus the weight and portability of the medicamentdispenser.

A variety of energy saving methods is available which generally involvereducing power consumption. One such method is to use a clock or timercircuit to switch the power on and off at regular or predeterminedintervals. In another method the system can selectively switch on/offspecific electronic components, such as visual display units or sensors,in order to power these devices only when they are required to perform aparticular sequence of events. Thus different electronic components maybe switched on and off at varying intervals and for varying periodsunder control of the system. The power sequencing system may alsorespond to a sensor, such as a motion or breath sensor, which isactivated on use of the device.

Low power or “micropower” components should be used within theelectronics where possible and if a high power device is required for aparticular function this should be put into a low power standby mode orswitched off when not required. Similar considerations apply in theselection of transducers. Operation at low voltage is desirable sincepower dissipation generally increases with voltage.

For low power digital applications complementary metal oxidesemi-conductor (CMOS) devices are generally preferred and these may bespecially selected by screening for low quiescent currents. Clock speedsof processors and other logic circuits should be reduced to the minimumrequired for computational throughput as power consumption increaseswith frequency. Supply voltages should also be kept at minimal valuesconsistent with reliable operation because power dissipation in charginginternal capacitance's during switching is proportional to the square ofthe voltage. Where possible, supply voltages should be approximately thesame throughout the circuit to prevent current flowing through inputprotection circuits. Logic inputs should not be left floating andcircuits should be arranged so that power consumption is minimised inthe most usual logic output state. Slow logic transitions areundesirable because they can result in relatively large class-A currentsflowing. Resistors may be incorporated in the power supply to individualcomponents in order to minimise current in the event of failure.

In some control applications, components that switch between on and offstates are preferred to those that allow analog (e.g. linear) controlbecause less power is dissipated in low resistance on states and lowcurrent off states. Where linear components are used (e.g. certain typesof voltage regulators) then types with low quiescent currents should beselected. In some circuit configurations it is preferable to useappropriate reactive components (i.e. inductors and capacitors) toreduce power dissipation in resistive components.

Suitably, the system additionally comprises a visual display unit fordisplay of data from the electronic processing means and/or electronicdata management system to the user. The display may for example,comprise a screen such as an LED or LCD screen. More preferably thevisual display unit is associable with the body of the medicamentdispenser.

Suitably, the medicament dispensing system additionally comprises adatalink for linking to a local data store to enable communication ofdata between the local data store and the electronic data managementsystem. The datastore may also comprise data management, data analysisand data communication capability.

The datastore may itself form part of a portable device (e.g. a handhelddevice) or it may be sized and shaped for accommodation within thepatient's home. The datastore may also comprise a physical storage areafor storage of replacement cassettes. The datastore may further comprisea system for refilling medicament from a reservoir of medicament productstored therewithin. The datastore may further comprise an electricalrecharging system for recharging any electrical energy store on themedicament dispenser, particularly a battery recharging system.

The datalink may for example enable linking with a docking station, apersonal computer, a network computer system or a set-top box by anysuitable method including a hard-wired link, an infrared link or anyother suitable wireless communications link.

In one aspect, the medicament dispensing system includes an electronicdose reminder system. This may be configured to have any suitable formand may be powered by mains, stored (e.g. battery) or self-regenerating(e.g. solar) energy power source.

The electronic dose reminder system comprises an electronic timer fortiming an elapsed time period corresponding to the time since the lastactuation of the device; a dose interval memory for storing datarelating to a prescribed dose interval time period; and a patientalerter for alerting a user. The alerter activates when the elapsed timeperiod exceeds the prescribed dose interval time period.

The electronic timer progressively times the period since the lastactuation of the medicament dispensing means (the ‘elapsed timeperiod’). The timer can have any suitable electronic form. Thesignificance of the ‘elapsed time period’ is that in use, it typicallycorresponds to the time elapsed since the previous dose delivery event.

The timer may be configured to include an automatic re-zeroing featuresuch that on subsequent actuation of the device the timer count startsagain from zero.

The dose interval memory stores data relating to a prescribed doseinterval time period. By way of examples, if the medicament is to betaken twice a day at a regular interval, the prescribed dose intervalmay be set as twelve hours, or for a once daily treatment the value maybe set at twenty four hours. In aspects, the system may be configured toallow for ready readjustment of the prescribed dose interval timeperiod, or it may be configured in secure fashion such that anyreadjustment may be made only by a designated prescriber (e.g. a medicalprofessional or pharmacist). Password and/or other security means may beemployed. The prescribed dose interval may be configured to be variableover a particular course of treatment, or alternatively it may be fixedat a set dose interval over the full course of treatment.

The patient alerter is designed to communicate an alert to the user. Thealerter activates only when the holding time period exceeds theprescribed dose interval time period. By way of an example, for a oncedaily treatment with a prescribed dose interval of twenty four hours,the alerter would activate only when the holding time period, as timedby the electronic timer, exceeds twenty four hours since at this pointanother dose is due to be taken. It may thus, be appreciated that thealerter acts functionally as a reminder to the patient that a dose isdue to be taken.

The alerter may in aspects, comprise a visual device, such as a liquidcrystal display (LCD) or an array of light-emitting diodes (LEDs),connected to a battery-driven timing device of any convenient kind knownto those skilled in the art. The visual device may be configured todisplay information such as the actual time or the elapsed time from thetaking of a previous dosage and may have superimposed thereon additionalmessages, such as a textual instruction to take a dose of themedicament. Alternatively, the instruction to take the medicament may beconveyed merely by displaying a warning colour or by causing the displayto flash or in any other way.

In a further alternative arrangement, no specific time or elapsed timeinformation is displayed, but the alerter merely provides a warningsignal that indicates the necessary action to the user.

Depending upon the lifestyle of the user, additional or alternativewarnings may be of greater assistance than purely visual warnings.Accordingly, it is envisaged that the alerter may provide audible and/ortactile warnings, such as vibration, instead of (or in addition to)visual warnings.

The alerter may provide a single, one-off alert. More preferably, thealerter is configured to provide the alert over a set period of time(the ‘alerting time period’ or ‘alerting window’). In one aspect, thealerting time period is calculated as a function of (e.g. fraction of)the dose interval time period. For example, for a twice-daily treatmentwith a dose interval time period of twelve hours, the alerting timeperiod may be set as half that period (i.e. six hours). In this case,the alert is then provided for the six hours immediately following theactivation of the alert.

The reminder system is typically configured such that the alertingsignal cuts off when the user removes the medicament delivery devicefrom the holder to enable dosing of medicament therefrom. The system isthen reset. Other manual cutoffs/overrides may also be included.

Suitably, the medicament dispensing system herein additionally comprisesan actuation detector for detecting actuation of the medicamentdispensing means, wherein said actuation detector transmits actuationdata to the electronic data management system.

The medicament dispensing means may additionally comprise a safetymechanism to prevent unintended multiple actuations. The patient isthereby, for example, protected from inadvertently receiving multipledoses of medicament in a situation where they take a number of shortrapid breaths. More preferably, the safety mechanism imposes a timedelay between successive actuations of the release means. The time delayis typically of the order of from three to thirty seconds.

Suitably, the medicament dispensing system additionally comprises arelease detector for detecting release of medicament from the medicamentdispensing means, wherein said release detector transmits release datato the electronic data management system.

Suitably, the medicament dispensing means additionally comprises a shakedetector for detecting shaking of the medicament container (e.g. priorto dispensing), wherein said shake detector transmits shake data to theelectronic data management system.

Suitably, any actuation detector, release detector, or shake detectorcomprises a sensor for detecting any suitable parameter such asmovement. Any suitable sensors are envisaged including the use ofoptical sensors. The release detector may sense any parameter affectedby release of the medicament such as pressure, temperature, sound,moisture, carbon dioxide concentration and oxygen concentration.

Suitably, the memory on the electronic data management system includes adose memory (e.g. look up table form) for storing dosage data andreference is made to the dose memory in calculating the optimum amountof medicament to dispense.

A suitable power source such as a battery, clockwork energy store, solarcell, fuel cell or kinetics-driven cell will be provided as required toany electronic component herein. The power source may be arranged to berechargeable or reloadable.

Suitably, the medicament dispensing system additionally comprises one ormore sensors for sensing environmental conditions, particularly thoseconditions which may affect the patient's therapeutic needs. Thus,ambient temperature, humidity, air pollution, ozone and other similarfactors may be sensed. The readings may simply be arranged for displayto the patient or in aspects, may be factored into the dosagecalculation, perhaps after receipt of a specific confirmation by thepatient that such factoring in is to be applied.

Suitably, the medicament dispensing system additionally comprises acommunicator for wireless communication with a network computer systemto enable transfer of data between the network computer system and theelectronic data management system. Dispensers employing suchcommunicators are described in pending PCT Applications Nos.PCT/EP00/09291 (PG3786), PCT/EP00/09293 (PG4029) and PCT/EP00/09292(PG4159). Preferably, the communicator enables two-way transfer of databetween the network computer system and the electronic data managementsystem.

Suitably, the data is communicable between the network computer systemand the electronic data management system in encrypted form. Allsuitable methods of encryption or partial encryption are envisaged.Password protection may also be employed. Suitably, the communicatoremploys radiofrequency or optical signals.

In one aspect, the communicator communicates via a gateway to thenetwork computer system. In another aspect, the communicator includes anetwork server (e.g. a web server) such that it may directly communicatewith the network.

In a further aspect, the communicator communicates with the gateway viaa second communications device. Preferably, the second communicationsdevice is a telecommunications device, more preferably a cellular phoneor pager. Preferably, the communicator communicates with the secondcommunications device using spread spectrum radiofrequency signals. Asuitable spread spectrum protocol is the Bluetooth (trade mark) standardwhich employs rapid (e.g. 1600 times a second) hopping between pluralfrequencies (e.g. 79 different frequencies). The protocol may furtheremploy multiple sending of data bits (e.g. sending in triplicate) toreduce interference.

In one aspect, the network computer system comprises a public accessnetwork computer system. The Internet is one suitable example of apublic access network computer system, wherein the point of accessthereto can be any suitable entrypoint including an entrypoint managedby an Internet service provider. The public access network computersystem may also form part of a telecommunications system, which mayitself be a traditional copper wire system, a cellular system or anoptical network.

In another aspect, the network computer system comprises a privateaccess network computer system. The private access network system mayfor example, comprise an Intranet or Extranet which may for example, bemaintained by a health service provider or medicament manufacturer. Thenetwork may for example include password protection; a firewall; andsuitable encryption means.

Preferably, the communicator enables communication with a user-specificnetwork address in the network computer system.

The user-specific network address may be selected from the groupconsisting of a web-site address, an e-mail address and a file transferprotocol address. Preferably, the user-specific network address isaccessible to a remote information source such that information fromsaid remote information source is made available thereto. Morepreferably, information from the user-specific network address can bemade available to the remote information source.

In one aspect, the remote information source is a medicament prescriber,for example a doctor's practice. Information transferred from themedicament prescriber may thus, comprise changes to prescriptiondetails, automatic prescription updates or training information.Information transferred to the medicament prescriber may comprisecompliance information, that is to say information relating to thepatient's compliance with a set-prescribing programme. Patientperformance information relating for example, to patient-collecteddiagnostic data may also be transferred to the medicament prescriber.Where the dispenser is an inhaler for dispensing medicament for therelief of respiratory disorders examples of such diagnostic data wouldinclude breath cycle data or peak flow data.

Suitably, the medicament dispensing system further comprises a samplingmeans. The sampling means is adapted to sample the patient's breath,skin, sweat, urine, blood or other bodily fluid. Suitably, the samplingmeans directs the patient's sample into the detecting means. Thesampling means may comprise for example a mouthpiece into which thepatient exhales or any other sampling means suitable for sampling theparticular fluid or bodily excretion.

The medicament dispensing system comprises medicament dispensing meansfor dispensing a quantity (e.g. volume or mass) of medicamentdeterminable by the electronic processing means. The quantity may inaspects, correspond to a full dose or it may correspond to a part dose.

Suitably, the medicament dispensing means comprises one or moremedicament container(s) for storing the medicament and one or moredispensing mechanism(s) for dispensing a quantity of medicamentdeterminable by the electronic processing means. The dispensing quantity(e.g. dose or part-dose) is in one aspect adjusted to an appropriatesetting by moving an adjustable actuator into appropriate positioncorresponding to the dosage required for the determined disease state orseverity.

The quantity of medicament to be dispensed (i.e. dose setting) is in oneaspect, automatically controlled by the micro-controller electronicallyvia an appropriate interface and electromechanical systems (or microelectromechanical system—MEMS).

In another aspect, the quantity of medicament to be dispensed is setmanually by the patient responsive to dose guidance determined by theelectronic processing means and indicated to the patient (e.g. visually,on an electronic display).

In one aspect, the quantity of medicament for dispensing is metered froma reservoir of medicament (e.g. in powder or fluid form) by use of anysuitable metering means.

Suitably, the meter comprises a valve (for example, a linear or rotaryvalve) and/or a piston and/or a load cell. In another aspect, the metercomprises a plunger, such as might exist in a syringe.

Suitably, the meter comprises at least one metering chamber. In oneembodiment, on actuation of the meter, the or each metering chambermoves into fluid communication with the reservoir.

In one embodiment, the meter and the reservoir are relatively rotatablewith respect to each other about a common central axis. Preferably, theor each metering chamber is adapted to be in fluid communicationselectively with the reservoir or with the patient.

The or each metering chamber may have a variable volume. Alternatively,the or each metering chamber may have a fixed volume which is variableby insertion of a plunger or piston. The or each metering chamber may beformed from expandable material and/or have a telescopic or concertinaarrangement.

In aspects, the medicament dispensing means is selected from the groupconsisting of a reservoir dry powder inhaler (RDPI), a multi-dose drypowder inhaler (MDPI), a metered dose inhaler (MDI) and a liquid sprayinhaler (LSI).

By reservoir dry powder inhaler (RDPI) it is meant an inhaler having areservoir form container pack suitable for containing multiple(un-metered doses) of medicament product in dry powder form andincluding means for metering medicament dose from the reservoir to adelivery position. The metering means may for example comprise ametering cup, which is movable from a first position where the cup maybe filled with medicament from the reservoir to a second position wherethe metered medicament dose is made available to the patient forinhalation.

By multi-dose dry powder inhaler (MDPI) is meant an inhaler suitable fordispensing medicament in dry powder form, wherein the medicament iscomprised within a multi-dose container pack containing (or otherwisecarrying) multiple, define doses (or parts thereof) of medicamentproduct. In a preferred aspect, the carrier has a blister pack form, butit could also, for example, comprise a capsule-based pack form or acarrier onto which medicament has been applied by any suitable processincluding printing, painting and vacuum occlusion.

In one aspect, the multi-dose pack is a blister pack comprising multipleblisters for containment of medicament product in dry powder form. Theblisters are typically arranged in regular fashion for ease of releaseof medicament therefrom.

In one aspect, the multi-dose blister pack comprises plural blistersarranged in generally circular fashion on a disc-form blister pack. Inanother aspect, the multi-dose blister pack is elongate in form, forexample comprising a strip or a tape.

Preferably, the multi-dose blister pack is defined between two memberspeelably secured to one another. U.S. Pat. No. 5,860,419 in the name ofGlaxo Group Ltd describes medicament packs of this general type. In thisaspect, the device is usually provided with an opening stationcomprising peeling means for peeling the members apart to access eachmedicament dose. Suitably, the device is adapted for use where thepeelable members are elongate sheets which define a plurality ofmedicament containers spaced along the length thereof, the device beingprovided with indexing means for indexing each container in turn. Morepreferably, the device is adapted for use where one of the sheets is abase sheet having a plurality of pockets therein, and the other of thesheets is a lid sheet, each pocket and the adjacent part of the lidsheet defining a respective one of the containers, the device comprisingdriving means for pulling the lid sheet and base sheet apart at theopening station.

By metered dose inhaler (MDI) it is meant a medicament dispensersuitable for dispensing medicament in aerosol form, wherein themedicament is comprised in an aerosol container suitable for containinga propellant-based aerosol medicament formulation. The aerosol containeris typically provided with a metering valve, for example a slide valve,for release of the aerosol form medicament formulation to the patient.The aerosol container is generally designed to deliver a predetermineddose of medicament upon each actuation by means of the valve, which canbe opened either by depressing the valve while the container is heldstationary or by depressing the container while the valve is heldstationary.

Where the medicament container is an aerosol container, the valvetypically comprises a valve body having an inlet port through which amedicament aerosol formulation may enter said valve body, an outlet portthrough which the aerosol may exit the valve body and an open/closemechanism by means of which flow through said outlet port iscontrollable.

The valve may be a slide valve wherein the open/close mechanismcomprises a sealing ring and receivable by the sealing ring a valve stemhaving a dispensing passage, the valve stem being slidably movablewithin the ring from a valve-closed to a valve-open position in whichthe interior of the valve body is in communication with the exterior ofthe valve body via the dispensing passage.

Typically, the valve is a metering valve. The metering volumes aretypically from 10 to 100 μl, such as 25 μl, 50 μl or 63 μl. Suitably,the valve body defines a metering chamber for metering an amount ofmedicament formulation and an open/close mechanism by means of which theflow through the inlet port to the metering chamber is controllable.Preferably, the valve body has a sampling chamber in communication withthe metering chamber via a second inlet port, said inlet port beingcontrollable by means of an open/close mechanism thereby regulating theflow of medicament formulation into the metering chamber.

The valve may also comprise a ‘free flow aerosol valve’ having a chamberand a valve stem extending into the chamber and movable relative to thechamber between dispensing and non-dispensing positions. The valve stemhas a configuration arid the chamber has an internal configuration suchthat a metered volume is defined therebetween and such that duringmovement between is non-dispensing and dispensing positions the valvestem sequentially: (i) allows free flow of aerosol formulation into thechamber, (ii) defines a closed metered volume for pressurized aerosolformulation between the external surface of the valve stem and internalsurface of the chamber, and (iii) moves with the closed metered volumewithin the chamber without decreasing the volume of the closed meteredvolume until the metered volume communicates with an outlet passagethereby allowing dispensing of the metered volume of pressurized aerosolformulation. A valve of this type is described in U.S. Pat. No.5,772,085.

By liquid spray inhaler (LSI) it is meant a medicament dispensersuitable for dispensing medicament in spray form, wherein the medicamentis typically formulated in liquid or solution form and comprised in aliquid container. The container is typically provided with a means ofmetering to a spray generator, which imparts energy to the liquid orsolution, thereby generating a spray for inhalation by the patient. Thespray generator, in aspects, comprises a vibrating element (e.g. a mesh)that provides vibrational energy to the formulation, thereby resultingin its aerosolisation. In other aspects, the spray generator comprises apump mechanism, which either delivers the medicament directly to thepatient (as a liquid spray) or which delivers the medicament to anintermediate position at which further energy is supplied thereto tofurther propel, aerosolise or otherwise direct the medicament dose tothe patient.

The dispensing mechanism controls the amount of drug released. Thisdosage control may be achieved via various control means. In one aspect,a valve, for example a metering valve is employed. Alternatively,drug-releasing membrane, drug containing capillaries, or otherreleasable captures can be used to adjust the amount of drug release inthe case of dry powders. Alternatively, regulation of the diameter ofthe medicament exit port may be used to regulate the quantity ofmedicament dispensed.

The dispensing mechanism suitable for the device includes, but is notlimited to the use of air jet (e.g. CO₂), vapour jet and acousticatomisation processes. Alternatively, mechanical vibration based onatomisation can be used to dispense aerosols. Other possible dispensingmeans may involve using ablation processes to generate aerosols, e.g.using ultrasonic pulsing or even a laser.

In particular aspects herein, the medicament dispensing system isprovided with plural medicament dispensing means, each for use in thedelivery of a component part of a combination medicament product. Thequantity of medicament dispensed by each medicament dispensing means isdeterminable by the electronic processing means, which thereby enablesthe delivery of ‘tailored’ combination products wherein the relativeamounts of each medicament component part thereof is variable inresponse to the patient's detected therapeutic need.

Suitably, the medicament dispensing system comprises first medicamentdispensing means and at least one further medicament dispensing means.

Suitably, the medicament dispensing system comprises

-   (a) a first medicament container for containing a first medicament    component and first release means for releasing the contents of said    first medicament container; and-   (b) at least one further medicament container for containing at    least one further medicament component and at least one further    release means for releasing the contents of each said at least one    further medicament container,    wherein the first medicament component is kept separate from the at    least one further medicament component until the point of release    thereof for delivery in combination.

Suitably, in combination, the first medicament and at least one furthermedicament comprise a combination product. That is to say, that whencombined together the distinct active medicament doses released byactuation of the device form a dose of a ‘multi-active’ medicamenttreatment.

On actuation, the combination medicament dispensing is designed todeliver a dose portion of the first medicament and a dose portion ofeach at least one further medicament. The term ‘dose portion’ isemployed because the distinct ‘portions’ are brought together ondelivery to form a combination (i.e. multi-active) product dose. Inaccord with the present invention, the ratio of incorporation of eachactive component of the combination is variable in response to inputfrom the electronic processing means.

In one particular aspect, the first medicament container contains pluralco-formulation compatible medicament components, and each at least onefurther medicament container contains at least one co-formulationincompatible medicament component.

The term ‘co-formulation compatible’ herein is used to mean compatiblein the sense of being amenable to co-formulation, perhaps evendisplaying synergetic co-formulation characteristics. The term‘co-formulation incompatible’ is used to mean the reverse, that is tosay for whatever reason including chemical or physical incompatibilityor simply lack of synergetic characteristics or benefits, the medicamentcomponents are either non-amenable to co-formulation or for whateverreason, including for development simplicity, preferably notco-formulated.

In a preferred embodiment, the system herein is designed to treat adisease by inhalation of medicament, either inhalation through the mouthor the nose. However, a system is also envisaged and is within the scopeof the invention, where the medicament is administered by an alternativemethod, for example by injection.

In use, the patient exhales (in the case of an inhalation system) intothe detecting means, one or more biochemical markers being present inthe exhaled breath. These biochemical markers are detected by thedetecting means which produces an output signal correlating with theconcentration of biochemical markers. It is possible that the detectingmeans is such that it is able to detect more than one biochemicalmarker. The output signal from the detecting means is processed by theelectronic processing means and will determine the severity of thedisease at that particular moment and the required dosage of drug ordrug combination. The electronic processing unit will programme thedispensing means such that when the patient takes his medication he willautomatically receive an appropriate quantity of medicament.

The invention will now be described in more detail with reference to thefollowing drawings:

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A, 1B and 1C show schematic representations of the system wherethe detecting means is integrated with the whole device, the detectingmeans is as an attachment to the device, and the detecting means isremote to the device.

FIG. 2 shows a schematic diagram of the various components of themedicament dispensing system.

DETAILED DESCRIPTION OF THE DRAWINGS

FIGS. 1A, 1B and 1C all show a schematic representation of themedicament dispensing system of the invention. The medicament dispensingsystem 10 comprises detecting means 20, electronic processing means 30and medicament dispensing means comprising medicament container 41 anddispensing mechanism 42. The detecting means comprises a sampling means(not shown) for example a mouthpiece into which a patient exhales.Specified biochemical markers in the exhaled breath are detected by thedetecting means 20 and the data processed by the electronic processingmeans 30. The electronic processing means 30 determines the requiredquantity of medication using the control and recording unit 50.Dispensing mechanism 42 dispenses the medication from medicamentcontainer 41 to the patient. In some cases, medicament container 41and/or dispensing mechanism 42 may be physically integrated with part ofthe detection means 20, e.g. a shared mouthpiece.

FIG. 2 shows a schematic functioning diagram of the system 110. Thedetecting means 120 may contain one or more sensing/transducing elementsof any suitable principles, including those for diagnostics sensing andthose for feedback for device control and referencing purposes. In thecase of an inhalation device, the detecting means is usually housed in amouthpiece. The signal conditioning and processing unit 131 includessignal pre-amplification and other necessary signal modificationcircuits before its converting to digital signal by control electronicsunit 130 (via A/D interface). This is a key unit consisting ofmicro-controller and affiliated electronics. The control electronic unit130 receives measurement signals, system control feedback, such astemperature, drug remaining in reservoir, actuator statues, and otherssystem parameters sending back by various sensors in the system. All theinformation is processed according the controlling software (or analoguecircuitry) developed for the system which tells the unit 130 to takeappropriate actions in responding to particular input signals. It alsocontrols system display unit 160 to display proper message for user, andcommunicates with other systems via telecommunication interface. It willinteract with database management software 170 to allow measurement datato be organised appropriately and to extract information required todetermine disease severity or dose required to deliver etc. Themedicament container 141 is basically a drug storage facility withnecessary sensors and actuators controllable by the micro-controller.Drug dispensing mechanism 142 is a (micro) mechanical orelectromechanical actuation system, which will respond to themicro-controller's signal to adjust drug-dispensing volume and activatesubsequent delivery actions.

The medicament dispensing system of the invention is suitable fordispensing medicament combinations, particularly for the treatment ofrespiratory disorders such as asthma and chronic obstructive pulmonarydisease (COPD), bronchitis and chest infections.

Appropriate medicaments may thus be selected from, for example,analgesics, e.g., codeine, dihydromorphine, ergotamine, fentanyl ormorphine; anginal preparations, e.g., diltiazem; antiallergics, e.g.,cromoglycate (e.g. as the sodium salt), ketotifen or nedocromil (e.g. asthe sodium salt); antiinfectives e.g., cephalosporins, penicillins,streptomycin, sulphonamides, tetracyclines and pentamidine;antihistamines, e.g., methapyrilene; anti-inflammatories, e.g.,beclomethasone (e.g. as the dipropionate ester), fluticasone (e.g. asthe propionate ester), flunisolide, budesonide, rofleponide, mometasonee.g. as the furoate ester), ciclesonide, triamcinolone (e.g. as theacetonide) or6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxy-androsta-1,4-diene-17β-carbothioicacid S-(2-oxo-tetrahydro-furan-3-yl) ester; antitussives, e.g.,noscapine; bronchodilators, e.g., albuterol (e.g. as free base orsulphate), salmeterol (e.g. as xinafoate), ephedrine, adrenaline,fenoterol (e.g. as hydrobromide), formoterol (e.g. as fumarate),isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine,pirbuterol (e.g. as acetate), reproterol (e.g. as hydrochloride),rimiterol, terbutaline (e.g. as sulphate), isoetharine, tulobuterol or4-hydroxy-7-[2-[[2-[[3-(2-phenylethoxy)propyl]sulfonyl]ethyl]amino]ethyl-2(3H)-benzothiazolone;adenosine 2a agonists, e.g.2R,3R,4S,5R)-2-[6-Amino-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-purin-9-yl]-5-(2-ethyl-2H-tetrazol-5-yl)-tetrahydro-furan-3,4-diol(e.g. as maleate); α₄ integrin inhibitors e.g.(2S)-3-[4-({[4-(aminocarbonyl)-1-piperidinyl]carbonyl}oxy)phenyl]-2-[((2S)-4-methyl-2-{[2-(2-methylphenoxy)acetyl]amino}pentanoyl)amino] propanoic acid (e.g. as free acid orpotassium salt), diuretics, e.g., amiloride; anticholinergics, e.g.,ipratropium (e.g. as bromide), tiotropium, atropine or oxitropium;hormones, e.g., cortisone, hydrocortisone or prednisolone; xanthines,e.g., aminophylline, choline theophyllinate, lysine theophyllinate ortheophylline; therapeutic proteins and peptides, e.g., insulin orglucagon; vaccines, diagnostics, and gene therapies. It will be clear toa person skilled in the art that, where appropriate, the medicaments maybe used in the form of salts, (e.g., as alkali metal or amine salts oras acid addition salts) or as esters (e.g., lower alkyl esters) or assolvates (e.g., hydrates) to optimise the activity and/or stability ofthe medicament.

Preferred respiratory medicaments are selected from albuterol,salmeterol, fluticasone propionate and beclomethasone dipropionate andsalts or solvates thereof, e.g., the sulphate of albuterol and thexinafoate of salmeterol.

Preferred medicament combination products contain salbutamol (e.g., asthe free base or the sulphate salt) or salmeterol (e.g., as thexinafoate salt) or formoterol (eg as the fumarate salt) in combinationwith an anti-inflammatory steroid such as a beclomethasone ester (e.g.,the dipropionate) or a fluticasone ester (e.g., the propionate) orbudesonide. A particularly preferred combination of components comprisesfluticasone propionate and salmeterol, or a salt thereof (particularlythe xinafoate salt). A further combination of components of particularinterest is budesonide and formoterol (e.g. as the fumarate salt).

Generally, powdered medicament particles suitable for delivery to thebronchial or alveolar region of the lung have an aerodynamic diameter ofless than 10 micrometers, preferably less than 6 micrometers. Othersized particles may be used if delivery to other portions of therespiratory tract is desired, such as the nasal cavity, mouth or throat.The medicament may be delivered as pure drug, but more appropriately, itis preferred that medicaments are delivered together with excipients(carriers) which are suitable for inhalation. Suitable excipientsinclude organic excipients such as polysaccharides (i.e. starch,cellulose and the like), lactose, glucose, mannitol, amino acids, andmaltodextrins, and inorganic excipients such as calcium carbonate orsodium chloride. Lactose is a preferred excipient.

Particles of powdered medicament and/or excipient may be produced byconventional techniques, for example by micronisation, milling orsieving. Additionally, medicament and/or excipient powders may beengineered with particular densities, size ranges, or characteristics.Particles may comprise active agents, surfactants, wall formingmaterials, or other components considered desirable by those of ordinaryskill.

The excipient may be included with the medicament via well-knownmethods, such as by admixing, co-precipitating and the like. Blends ofexcipients and drugs are typically formulated to allow the precisemetering and dispersion of the blend into doses. A standard blend, forexample, contains 13000 micrograms lactose mixed with 50 microgramsdrug, yielding an excipient to drug ratio of 260:1. Dosage blends withexcipient to drug ratios of from 100:1 to 1:1 may be used. At very lowratios of excipient to drug, however, the drug dose reproducibility maybecome more variable.

Aerosol formulations suitable for use with metered dose inhaler (MDI)dispensers typically comprise a propellant. Suitable propellants includeP11, P114 and P12, and the CFC-free hydrofluoroalkane propellantsHFA-134a and HFA-227.

The MDI aerosol formulation may additionally contain a volatile adjuvantsuch as a saturated hydrocarbon for example propane, n-butane,isobutane, pentane and isopentane or a dialkyl ether for exampledimethyl ether. In general, up to 50% w/w of the propellant may comprisea volatile hydrocarbon, for example 1 to 30% w/w. However, formulations,which are free or substantially free of volatile adjuvants arepreferred. In certain cases, it may be desirable to include appropriateamounts of water, which can be advantageous in modifying the dielectricproperties of the propellant.

A polar co-solvent such as C₂₋₆ aliphatic alcohols and polyols e.g.ethanol, isopropanol and propylene glycol, preferably ethanol, may beincluded in the MDI aerosol formulation in the desired amount to improvethe dispersion of the formulation, either as the only excipient or inaddition to other excipients such as surfactants. Suitably, the drugformulation may contain 0.01 to 30% w/w based on the propellant of apolar co-solvent e.g. ethanol, preferably 0.1 to 20% w/w e.g. about 0.1to 15% w/w. In aspects herein, the solvent is added in sufficientquantities to solubilise the part or all of the medicament component,such formulations being commonly referred to as solution formulations.

A surfactant may also be employed in the MDI aerosol formulation.Examples of conventional surfactants are disclosed in EP-A-372,777. Theamount of surfactant employed is desirable in the range 0.0001% to 50%weight to weight ratio relative to the medicament, in particular, 0.05to 5% weight to weight ratio.

The final aerosol formulation desirably contains 0.005-10% w/w,preferably 0.005 to 5% w/w, especially 0.01 to 1.0% w/w, of medicamentrelative to the total weight of the formulation.

The medicament dispensing system of the invention is in one aspectsuitable for dispensing medicament for the treatment of respiratorydisorders such as disorders of the lungs and bronchial tracts includingasthma and chronic obstructive pulmonary disorder (COPD). In anotheraspect, the invention is suitable for dispensing medicament for thetreatment of a condition requiring treatment by the systemic circulationof medicament, for example migraine, diabetes, pain relief e.g. inhaledmorphine.

Accordingly, there is provided the use of a medicament dispensing systemaccording to the invention for the treatment of a respiratory disorder,such as asthma and COPD. Alternatively, the present invention provides amethod of treating a respiratory disorder such as, for example, asthmaand COPD, which comprises administration by inhalation of an effectiveamount of medicament product as herein described from a medicamentdispensing system of the present invention.

It will be understood that the present disclosure is for the purpose ofillustration only and the invention extends to modifications, variationsand improvements thereto.

The application of which this description and claims form part may beused as a basis for priority in respect of any subsequent application.The claims of such subsequent application may be directed to any featureor combination of features described therein. They may take the form ofproduct, method or use claims and may include, by way of example andwithout limitation, one or more of the following claims:

1. A medicament dispensing system for treatment of a disease, the systemcomprising: (i) detecting means for detecting one or more biochemicalmarker(s) indicative of said disease; (ii) electronic processing meansfor processing information obtainable from the detecting means; and(iii) medicament dispensing means for dispensing a quantity ofmedicament determinable by the electronic processing means.
 2. Amedicament dispensing system according to claim 1, wherein the detectingmeans, electronic processing means and medicament dispensing means areintegrated in a single device.
 3. A medicament dispensing systemaccording to claim 1, wherein the electronic processing means andmedicament dispensing means are integrated in a single device, and thedetecting means is an attachment to the device.
 4. A medicamentdispensing system according to claim 1, wherein the electronicprocessing means and medicament dispensing means are integrated in asingle device, and the detecting means is remote to the device.
 5. Amedicament dispensing system according to claim 1, wherein the detectingmeans and medicament dispensing means are integrated in a single device,and wherein the electronic processing means exists as a standalone unit.6. A medicament dispensing system according to claim 1, wherein thedetecting means comprises a sensing means.
 7. A medicament dispensingsystem according to claim 6, wherein the sensing means comprises abiosensor.
 8. A medicament dispensing system according to claim 7,wherein said biosensor comprises a sensing layer and a transducer layer.9. A medicament dispensing system according to claim 8, wherein saidsensing layer comprises one or more materials selected from the groupconsisting of enzymes, receptors, micro-organisms, antibodies, antigens,nucleic acids, cells, peptides, proteins and biochemicals.
 10. Amedicament dispensing system according to claim 8, wherein the sensinglayer comprises one or more artificial or synthetic materials analogousto enzymes, receptors, micro-organism, antibodies, antigens, nucleicacids, cells, peptides, proteins and biochemicals.
 11. A medicamentdispensing system according to claim 8, wherein the sensing layercomprises a renewable sensing surface.
 12. A medicament dispensingsystem according to claim 7, wherein the sensing layer comprises anon-renewable sensing surface.
 13. A medicament dispensing systemaccording to claim 12, wherein the sensing layer comprises a disposablecomponent incorporating the non-renewable sensing surface.
 14. Amedicament dispensing system according to claim 8, wherein saidtransducer layer comprises an optical, electrical, semi-conductor,thermal or acoustic mechanism.
 15. A medicament dispensing systemaccording to claim 6, wherein the sensing means is a non-specific bio-or chemosensor.
 16. A medicament dispensing system according to claim15, wherein the detecting means further comprises a pre-separationdevice.
 17. A medicament dispensing system according to claim 16,wherein the pre-separation device comprises a miniaturised gaschromatograph device, a capillary electrophoresis chip or otherelectrophoresis device, or a lateral flow membrane.
 18. A medicamentdispensing system according to claim 1, wherein the detecting meanscomprises spectroscopic detecting means for direct spectroscopicdetection of one or more biochemical marker(s).
 19. A medicamentdispensing system according to claim 18, wherein the spectroscopicdetection means is suitable for use in infra red and Raman spectroscopicdetection methods.
 20. A medicament dispensing system according to claim1, comprising plural detecting means for detecting one or morebiochemical marker(s).
 21. A medicament dispensing system according toclaim 20, wherein said plural detecting means are arranged in arrayfashion.
 22. A medicament dispensing system according to claim 1,further comprising sampling means for sampling a patient's breath,wherein the detecting means is located within said sampling means.
 23. Amedicament dispensing system according to claim 1, wherein theelectronic processing means comprises a micro-controller with associatedanalogue and digital electronics and interfaces.
 24. A medicamentdispensing system according to claim 23, wherein the electronicprocessing means further comprises an amplifier for amplifying thesignal received from the detecting means.
 25. A medicament dispensingsystem according to claim 1, additionally comprising an electronic datamanagement system in communication with the electronic processing means.26. A medicament dispensing system according to claim 25, wherein theelectronic data management system includes a database and the electronicprocessing means makes reference to that database in determining thequantity of medicament for dispensing.
 27. A medicament dispensingsystem according to claim 1, wherein the medicament dispensing meanscomprises a medicament container and a dispensing mechanism.
 28. Amedicament dispensing system according to claim 27, wherein thedispensing mechanism is automatically set in direct response to thedetermination of the electronic processing means.
 29. A medicamentdispensing system according to claim 27, wherein the dispensingmechanism is set manually in response to the determination of theelectronic processing means.
 30. A medicament dispensing systemaccording to claim 1, wherein the medicament dispensing means isselected from the group consisting of a reservoir dry powder inhaler(RDPI), a multi-dose dry powder inhaler (MDPI), a metered dose inhaler(MDI) and a liquid spray inhaler (LSI).
 31. A medicament dispensingsystem according to claim 1, comprising plural medicament dispensingmeans, each for use in the delivery of a component part of a combinationmedicament product.
 32. A medicament dispensing system according toclaim 31, wherein the dispensing ratio of each component part of thecombination medicament product is variable in response to input from theelectronic processing means.
 33. A medicament dispensing systemaccording to claim 31 comprising: (a) a first medicament container forcontaining a first medicament component and first release means forreleasing the contents of said first medicament container; and (b) atleast one further medicament container for containing at least onefurther medicament component and at least one further release means forreleasing the contents of each said at least one further medicamentcontainer, wherein the first medicament component is kept separate fromthe at least one further medicament component until the point of releasethereof for delivery in combination.
 34. The use of a medicamentdispensing system as claimed in claim 1 for the treatment of a disease.35. The use according to claim 34, wherein the disease to be treated isa respiratory disorder.
 36. A method of treating a respiratory disorder,which comprises the use of a medicament dispensing system as claimed inclaim
 1. 37. The use according to claim 34, wherein the disease to betreated is a condition requiring systemic circulation of a medicament.38. A method of treating a condition requiring systemic circulation of amedicament, which comprises the use of a medicament dispensing system asclaimed in claim 1.